Peptide constructs for treating autoimmune and related diseases

Abstract

Conjugated peptides include a first peptide component which is an antigen associated with autoimmune disease, allergy, asthma or transplantation rejection and binds to an antigen-specific receptor on a T cell, and a second peptide component which corresponds to an “antigen presenting molecule”, namely, a peptide binding to a T cell surface receptor, which would normally promote T cell activation when the first peptide is bound to its antigen-specific T cell receptor. However, in this invention, the second peptide component has an amino acid sequence which is a modification of an antigen presenting T cell binding peptide, such modification blocking or inhibiting the engagement of receptor sites on the T cell surface (other than the antigen-specific T cell receptor). As a result, T cell activation is prevented, and is directed through antigen-specific T cell receptor occupation, without T cell activation, leading to antigen-specific T cell anergy and cell death. Administration of the conjugated peptide to an animal will provide protection against disease associated with the first peptide component, resulting from the elimination of the T cells bearing the antigen-specific receptors for that anti genic peptide. The conjugated peptides of this invention provide antigen-specific protection without impairing the immune response to other antigens.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of International application PCT / US00 / 41647 filed Oct. 27, 2000, and U.S. Provisional Application No. 60 / 161,733, filed Oct. 27, 1999.BACKGROUND OF THE INVENTION[0002](1) Field of Invention[0003]The present invention relates to a conjugated peptide for conferring protection against autoimmune diseases, such as, for example, myocarditis and autoimmune thyroid disease, allergic diseases, asthma, host-versus graft and graft-versus-host disease. The present invention also relates to a method for treating or inhibiting development of autoimmune diseases, asthma, allergy, and tissue transplantation rejection and to conjugated peptides and compositions which may be used to carry out said method.[0004](2) Background of the Invention[0005]A technique for modulating T cell immunological responses to a wide range of antigenic peptides has been described in the literature. This technology, referred to as LEAPS™, pr...

AI Technical Summary

Benefits of technology

[0008]It has now been discovered by the present inventor that the TCBL peptide component may be modified to prevent induction of the second signal necessary for the activation of T cells, thereby inhibiting the initiation of an immune response. Thus, the antigenic peptide component of the resulting conjugated peptide will retain its ability to interact with its receptor (antigen-specific binding site) on the T-cell, while at the same time preventing the modified TCBL peptide portion from attaching to the TCBL receptor on the same T cell surface.

[0010]Thus, the present invention provides a new class of conjugated peptides comprised of two different covalently bonded peptide components, one peptide component being an antigen associated with autoimmune disease, asthma, allergy or transplantation rejection, and the second peptide component being a T cell binding ligand modified to inhibit or suppress the activation of the class or subclass of T cells to which the antigenic peptide component selectively binds, whereby the conjugated peptide will markedly decrease or completely retard undesirable immune response outcomes (e.g., autoimmune disease, asthma or allergy or transplantation rejection), while maintaining the remainder of the immune response intact.

Problems solved by technology

This outcome is desired due to the fact that antigen-specific response by T cells and other cells may, in many instances, lead to an undesirable immune response outcome culminating in autoimmune disease (in the case of autoantigens), asthma and allergy (in the case of allergens) and transplantation rejection (in the case of transplantation antigens).

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